Sutures and staples are the main tissue attachment and closure techniques currently in use. However, these techniques can damage tissue due to deep piercing and expose it to tension forces that easily tear friable tissues. Suture application is also time-consuming and an invasive process, impeding the development of next generation, minimally invasive surgical procedures.
Biodegradable tissue adhesives for internal use offer a potential solution. These adhesives can be applied directly to a tissue surface and promote an immediate closure of an internal defect. However, the introduction of this approach into the clinic has been challenging given the lack of materials that can promote strong wet adhesion without exacerbated inflammatory and/or toxic responses.
Medical grade cyanoacrylates (CA) adhere strongly to tissue upon exposure to water or other basic compounds. Despite several attempts to improve its performance and biocompatibility through changes in the CA monomers chemical composition, however, its use has been mostly limited to external applications (e.g., on the skin) given the induced inflammatory and toxic responses. This derives from its reactivity towards functionalities on the tissue surface, the exothermic nature of the reaction and, more importantly, the release of formaldehyde and cyanoacetate during the degradation of the material.
U.S. Patent Application Publication No. 2011/0021965 describes biodegradable and biocompatible tissue adhesives based on a combination of nanotopography and mild surface chemistry. A layer of dextran-aldehyde glue is used to coat the nanotextured surface enabling adhesion in wet environments. WO 2012/030570 describes articles containing substantially cylindrical protrusions in combination with a surface treatment. The protrusions contain a stiff resin having a Young's modulus greater than 17 MPa. Both the '965 application and the '579 application describe performance by measuring the shear adhesion. However, the forces achieved were too low for most clinical applications.
There is a need for improved adhesive systems that exhibit 90° pull off adhesive strengths that are suitable for clinical applications. There is moreover a need for improved adhesive systems that allows for the use of tissue adhesives, the use of which in the clinic, absent the present system, is associated with adverse effects, such as for example inflammatory or toxic responses.
Therefore, it is an object of the invention to provide adhesive systems that exhibit 90° pull off adhesive strengths that are suitable for clinical applications and methods of making and using thereof.
Another object of the invention is to provide adhesive systems that exhibit 90° pull off adhesive strengths that are suitable for clinical applications while minimizing the toxicity issues/adverse side effects and/or adverse reactivity associated with tissues adhesives and methods of making and using thereof.